Abstract This US-China collaborative study will leverage extensive data and archived biospecimens from two well- established prospective birth cohorts: one in Boston, US; and the other in Shanghai, China, to examine the temporal and dose-response relationships between maternal exposure to Hg at critical developmental windows (preconception and specific trimesters) and child cardio-metabolic outcomes from birth to age 21 years. This proposal has a strong scientific premise. Hg is a persistent and widespread environmental pollutant worldwide and a known neurotoxicant at high doses, and its role in cardio-metabolic health is beginning to be recognized. Studies in adults have suggested that low dose Hg exposure was associated with cardiovascular diseases, diabetes, and obesity. A critical unanswered question is whether maternal prenatal low dose Hg exposure can have a long-lasting impact on the developing fetus. This proposal presents a prime opportunity for a US-China collaboration on environmental health since US and China are among the top emitters of Hg in the world. This proposal focuses on the effect of in-utero Hg exposure on child?s long-term cardio-metabolic health, which is novel, important, and critically needed, given Hg?s ability to cross the placenta and the well- documented fetal bioaccumulation of Hg. Our preliminary data showed a very high correlation of maternal-cord blood Hg and a dose-response relationship between maternal Hg levels and child BMI and blood pressure. These findings raise the hypothesis that maternal low dose prenatal exposure to Hg affects fetal future cardio- metabolic health and warrant further investigation. This proposal uses vigorous scientific methods. Both the US and China lack clear and effective strategies to reduce the adverse health effects of low dose Hg exposure. We plan to evaluate to what extent maternal micronutrient status (e.g., folate) counteracts the adverse effects of Hg exposure on child cardio-metabolic outcomes based on our preliminary data. Furthermore, motivated by our preliminary data that maternal Hg exposure can alter both maternal and fetal circulating metabolomic profile, we will explore maternal and fetal metabolome to gain novel insight to mechanistic pathways. This proposal provides an exceptional platform for US-China scientists to leverage resources and expertise on both sides. The two cohorts can serve as a discovery and replication cohort for each other as well as meta-analysis, using a similar study design and outcome and covariate definitions; and same laboratory and quality assurance and control (QA/QC) procedures and statistical methods. By doing so, it greatly enhances our ability to test the study hypotheses and make the study findings far more generalizable and impactful. This proposal has significant clinical and public health implications. It represents a significant step forward in elucidating the roles of prenatal exposure to low dose Hg and micronutrients in child long-term cardio-metabolic outcomes, as well as the potential mechanisms. If successful, it can serve as a model to rigorously investigate other early life environmental exposures.